Oral osmotic systems have been known in the art for some time, being initially developed by Alza Corp. in the late 1970's. Since then there have been a number of variations on the general theme reported in both the patent and scientific literature. Of special significance to the present invention is U.S. Pat. No. 4,857,336 ('336), issued to Khanna on Aug. 15, 1989, which is incorporated in toto herein by reference. This patent discloses carbamazepine oral osmotic systems having a core of carbamazepine, hydroxypropylmethyl cellulose as a crystal habit modifier for carbamazepine, mannitol as an osmotic driving agent, two different grades of hydroxyethyl cellulose (in a 1:1 weight ratio) as the core matrix polymers, lubricant and wetting agent; and a semipermeable wall with a bore connecting the core and the outer environment. The present invention is an improvement of the '336 invention with respect to carbamazepine and other slightly soluble agents. While the '336 disclosed examples can be prepared to deliver reasonable carbamazepine amounts over time in the desired fashion, the instant invention possesses a number of distinct advantages.
First, other '336 formulations than that described above require a two step manufacturing process utilizing two organic solvents to prepare the core. From a manufacturing cost and environmental standpoint, it would be highly desirable to reduce the processing steps and avoid the use of organic solvents as much as possible.
Secondly, with those other core formulations, end point detection in the granulation steps is difficult resulting in insufficient or excess solvents being used. Excessive solvent in the granulation results in an unsuitable pasty mass rather than a granulation acceptable for compression into cores.
While Example 4 of '336 has been found to be processable in a single granulation step, avoiding the cost disadvantages, and resulting in reducing the amount of organic solvent use, that formulation does not deliver carbamazepine as desired.